Long-term effects of pubertal stressors on female sexual receptivity and estrogen receptor-α expression in CD-1 female mice

Abstract

Exposure to stress during puberty can lead to long-term behavioral alterations. Female mice, of the inbred C57BL/6 strain, have been shown to display lower levels of sexual receptivity in adulthood when exposed to shipping stress or to an immune challenge during puberty. The present study investigated whether this effect can be extended to CD1 outbred mice and examined a possible mechanism through which exposure to stressors could suppress sexual receptivity. The results revealed that CD1 mice injected with lipopolysaccharide (LPS) or exposed to shipping stress at 6 weeks old display lower levels of sexual receptivity in response to estradiol and progesterone in adulthood than control mice. Moreover, mice exposed to shipping stress at 8 weeks old also displayed reduced sexual receptivity, but those injected with LPS at that time showed slightly reduced effects, suggesting that the sensitive pubertal period extends to 8 weeks of age in this strain of mice. The examination of estrogen receptor-α (ER-α) expression revealed that mice exposed to shipping stress during the sensitive period (6 weeks) display lower levels of ER-α expression in the medial preoptic area and the ventromedial nucleus and the arcuate nucleus of the hypothalamus than mice shipped at a younger age. These findings support the prediction that exposure to shipping stress or LPS during puberty decreases behavioral responsiveness to estradiol and progesterone in adulthood in an outbred strain of mice through enduring suppression of ER-α expression in some brain areas involved in the regulation of female sexual behavior.

Figure 1

Plates from the Franklin and Paxinos (1997) mouse brain atlas depicting brain regions analyzed (shaded in gray) for expression of ER-α. Medial preoptic area (MPOA), ventromedial nucleus (VMN), paraventricular nucleus (PVN) and arcuate nucleus (Arc) of the hypothalamus. Oval and rectangular frames were drawn to set the boundaries of these areas.

Figure 2

A) Sickness score (Mean ± SEM) and B) Percent body weight (Mean ±SEM) change in mice treated with either saline or LPS at six or eight weeks old. *p < 0.05

Figure 3

Lordosis quotient (Mean ± SEM) on weekly Test 4 and Test 5 of mice treated with either saline or LPS at six or eight weeks old. *p < 0.05

Figure 4

Lordosis quotient (Mean ± SEM) of mice shipped at 3, 4, 6, 8 and 10 weeks old on Test 4 and Test 5. a: lordosis quotient significantly lower than females shipped at three weeks old (p < 0.05). b: significantly lower than females shipped at four weeks old (p < 0.05). c: significantly lower than females shipped at 10 weeks old (p < 0.05).

Figure 5

Lordosis quotient (Mean ± SEM) on Test 1 and Test 2 of mice shipped at four or six weeks old. *p < 0.05

Figure 6

A) Photomicrographs and B) Number of ER-α IR cells in females shipped at four or six weeks old in the arcuate nucleus (Arc), anteroventral paraventricular nucleus (AVPV), medial preoptic area (MPOA) and ventromedial nucleus of the hypothalamus (VMN).